Breast cancer is one of the most common tumor types in the Western world, affecting more than every tenth woman (1). One fourth of all malignant diagnoses are for breast cancer and since late 1990 the incidence worldwide, especially for the age group 45 to 70, has been increasing, although there has been a slight decline during the past few years. One explanation for the decrease is that early screening activities (mammography) and endocrine and cytostatic therapies have improved survival.
In spite of this decline, breast cancer still kills over one hundred women every day in the United States. Furthermore, despite improvements in early detection and understanding of the molecular basis of breast cancer, approximately 30% of all patients with primary breast cancer will develop distant recurrence of the disease (i.e. metastasis) (2).
Once metastatic disease develops, the possibility of a cure is very limited or non-existing. To offer better treatments with an increased efficacy and lower toxicity, therapies must be selected based on the clinical and molecular characteristics of the tumor. Today, there are only limited possibilities to predict disease outcome using traditional clinical predictors, such as histological grade and lymph node status (3, 4).
Recently, genomic studies have opened up the possibility to identify patients with poor prognosis regarding recurrence-free survival, using expression analysis of a multitude of different genes (5, 6). However, despite tremendous efforts it is presently not possible to perform risk assessments for breast cancer metastasis using a simple blood test, although recent developments in affinity proteomics have advanced the field of cancer biomarkers (7-9). Serum is a particularly valuable source, since it is not only useful for the initial screen of the disease but could also be used for continuous monitoring and analysis of therapy efficacy, which is in contrast to predictors based on measurements performed at the time of surgery.
Hence, there exists a need for improved methods for the prognosis of breast cancer and, in particular, the risk of developing distant recurrence of the disease (i.e. metastasis).
Against this background, the present inventors have now developed a proteomic, serum-based approach to prognosis breast cancer and identified a series of serum biomarkers for determining the risk of developing distant recurrence of the disease (i.e. metastasis).